Objective. To assess the relationship between acculturation and clinical, socioeconomic-demographic, and behavioral/psychosocial features in Hispanic patients with systemic lupus erythemotosus (SLE) from the LUMINA (Lupus in Minority Populations, Nature versus Nurture) cohort. Methods. An empirically derived questionnaire was administered to 67 Mexican American SLE patients participating in a longitudinal study of outcome. This questionnaire inquired about place of birth, upbringing and length of stay in the United States, language (proficiency, usage, and preferences; English/bilingual versus Spanish;, type of neighborhood, self-identity, and social interactions. Responses to this questionnaire and an informal interaction with a single bilingual, bicultural Mexican American research assistant were used to generate a score on a 10-cm anchored visual analog scale (VAS) (0 = no acculturation and 10 = maximum acculturation). The responses to the questionnaire were then quantified and scored by a physician who was unaware of the VAS. A composite score was then obtained utilizing 4 of the 6 components of the instrument. The VAS was found to have adequate sensitivity (91%), specificity (88%), and overall predictive value (89%) when the composite score was used as the validity criterion. Therefore, the VAS was used in all subsequent analyses; the median in this VAS separated patients into high and low acculturation groups. The relationship between acculturation and sociodemographic, behavioral/psychosocial (social support, abnormal illness-related behaviors, and helplessness) and clinical variables (disease duration, onset type, number of American College of Rheumatology criteria met, disease activity, and damage) at study entry was then explored. Results. Patients in the low acculturation group had fewer years of education, were less likely to have private health insurance, and had less social support as compared with those in the high acculturation group; they also exhibited less disease activity as determined by the overall physician and patient global assessments of the Systemic Lupus Activity Measure. Abnormal illness-related behaviors and helplessness were not increased in the low acculturation group. Conclusions. Low levels of acculturation were associated with indicators of low socioeconomic status, but also with less disease activity at enrollment into LUMINA; they were, however, not associated with more abnormal illness-related behaviors or with helplessness, as measured in this study. The possible impact of acculturation and of its mediators in the course and outcome of SLE among Hispanic patients needs to be determined longitudinally.